There are an estimated 430,000 Alzheimer's disease patients in Florida, with the Tampa Bay and Miami/Dade County areas having a large, ethnically diverse and growing population with this illness. Indeed, Florida is the fourth largest state in the country in terms of population, and the second largest in total number of Alzheimer's disease patients. Clearly Florida would be ideal place to site an NIA-funded Alzheimer's disease Research Center (ADRC). Yet no such Florida-based ADRC exists. Therefore, a group of researcher s and physicians from across the state have joined together to design and seek funding for the Florida ADRC (FADRC) described in this application. The general goals of the proposed FADRC are represented by the three Projects which aim: 1. To better understand the process of transition from normal to MCI to AD by determining which combinations of clinical, epidemiologic, imaging, neuropsychological, and biological markers best identify individuals who will experience a rapid rate of cognitive decline toward AD or other dementing illnesses. 2. To investigate the ability of cognitive rehabilitation to intervene in and slow disease progression in MCI and early AD patients. 3. To use mouse models of AD to determine which aspects of environmental enrichment (including cognitive rehabilitation) best slow or reverse cognitive impairment and might be similarly applied to human patients. These projects are mutually supportive and synergistic because markers found in Project 1 can be used to measure success and/or to distinguish populations in Project 2, and model results obtained in Project 3 can be used to help decide which type of intervention may be most successful in humans. The three projects are supported by 5 Cores- Clinical, Data Management, Neuropathology, Education, and Mouse Behavior and Neuropathology. The end result of the synergy inherent in the design of the FADRC may be the development a novel therapeutic intervention that can slow the clinical course of the disease. To aid in the development, administration and financial support of the planned FADRC, in 2002, the Florida Legislature established and funded the Johnnie B. Byrd Sr. Alzheimer's Center and Research Institute on the campus of the University of South Florida. Byrd Institute funds and personnel will be used to supplement the NIA grant in a State-Federal collaboration that will help assure the success of the proposed FADRC.